Investigation of Brain Network Dynamics in Depression
| Status: | Completed |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 4/2/2016 |
| Start Date: | February 2013 |
| End Date: | September 2015 |
| Contact: | Mark C Eldaief, M.D. |
| Email: | meldaief@partners.org |
| Phone: | (617) 732-8060 |
Investigation of Cortico-limbic Networks and Their Dynamics in Major Depressive Disorder
This research study is being done to gain a better understanding about brain networks that
may be involved in depression. The investigators plan to examine how these networks change
after the brain is stimulated with "Transcranial Magnetic Stimulation" (TMS). TMS is a way
of stimulating the brain in order to mildly activate or mildly suppress different brain
areas, and is used to treat some forms of depression. It is hoped that this study will
facilitate learning more about the structure and function of different brain areas and the
ways that they are interconnected to form networks, both in depressed people and in people
without depression. In this research study, the effects of TMS will be measured by obtaining
"pictures" of the brain with "Magnetic Resonance Imaging" (MRI) and with "Positron Emission
Tomography" (PET). More specifically, this will be accomplished with a combined MRI and PET
scanner, which is capable of simultaneously obtaining both MRI and PET images of the brain.
This scanning paradigm will allow the assessment of local metabolic changes resulting from
TMS (with PET images) and brain network changes resulting from TMS (with fMRI). Changes
resulting from TMS between 20 subjects with depression and 20 healthy volunteers will be
calculated and will form the main outcome measure.
may be involved in depression. The investigators plan to examine how these networks change
after the brain is stimulated with "Transcranial Magnetic Stimulation" (TMS). TMS is a way
of stimulating the brain in order to mildly activate or mildly suppress different brain
areas, and is used to treat some forms of depression. It is hoped that this study will
facilitate learning more about the structure and function of different brain areas and the
ways that they are interconnected to form networks, both in depressed people and in people
without depression. In this research study, the effects of TMS will be measured by obtaining
"pictures" of the brain with "Magnetic Resonance Imaging" (MRI) and with "Positron Emission
Tomography" (PET). More specifically, this will be accomplished with a combined MRI and PET
scanner, which is capable of simultaneously obtaining both MRI and PET images of the brain.
This scanning paradigm will allow the assessment of local metabolic changes resulting from
TMS (with PET images) and brain network changes resulting from TMS (with fMRI). Changes
resulting from TMS between 20 subjects with depression and 20 healthy volunteers will be
calculated and will form the main outcome measure.
Repetitive transcranial magnetic stimulation (rTMS), when delivered to the dorsolateral
prefrontal cortex (DLPFC) is a clinically effective treatment for major depressive disorder
(MDD). Network models of MDD are increasingly gaining acceptance, and functional
connectivity MRI (fcMRI) has revealed topographically specific aberrations in functional
network architecture in MDD. And yet, despite hints that the therapeutic effects of rTMS are
actuated through distributed impacts upon cortical and subcortical limbic centers, the
network effects of rTMS remain mysterious. This study seeks to investigate the way rTMS to
DLPFC modulates network functional connectivity between the site of stimulation and a
critical limbic region, the subgenual cingulate (sgACC), and between the sgACC and other
limbic regions. In this study, high frequency rTMS will be used to stimulate the left DLPFC
(recapitulating the therapeutic methodology), specifically, regions of the DLPFC that are
functionally correlated and anti-correlated with the sgACC. This will be accomplished in a
group of patients with MDD, and in a group of carefully matched controls. These subjects
will be scanned before and after rTMS is delivered, as a way of gauging its effects. The
feasibility of this design was recently demonstrated by our group (Eldaief et al. PNAS
2011). Changes induced by the stimulation will be charted with a novel combined MRI-PET
(Positron Emission Tomography) scanner at the MGH Martinos Center, which is capable of
simultaneously recording fcMRI BOLD (Blood oxygenation level-dependent) and
18Flurodeoxyglucose (FDG) PET data. This will permit cortico-limbic networks to be
characterized dynamically through (1) examination of the differential effects of stimulating
two networks in the DLPFC, and (2) by tracking the dynamic interplay between rTMS induced
changes in local glucose metabolism at DLPFC and sgACC on the one hand, and changes in
distributed connectivity between these regions on the other. In an exploratory aim, MDD
patients will return three months later (after they have undergone a non-specific treatment
intervention with their psychiatric provider) for the identical rTMS/fcMRI/FDG-PET
procedures. This aim will establish, as proof of principle, that treatment of MDD is
associated with changes in cortico-limbic functional network architecture, and in
cortico-limbic dynamics. Eventually, it is hoped that this work will lead to the emergence
of aberrant cortical dynamics as a biomarker for MDD. In addition, this work might pollinate
future studies which use aberrant cortical dynamics as a novel therapeutic target upon which
neuromodulatory interventions might intervene.
prefrontal cortex (DLPFC) is a clinically effective treatment for major depressive disorder
(MDD). Network models of MDD are increasingly gaining acceptance, and functional
connectivity MRI (fcMRI) has revealed topographically specific aberrations in functional
network architecture in MDD. And yet, despite hints that the therapeutic effects of rTMS are
actuated through distributed impacts upon cortical and subcortical limbic centers, the
network effects of rTMS remain mysterious. This study seeks to investigate the way rTMS to
DLPFC modulates network functional connectivity between the site of stimulation and a
critical limbic region, the subgenual cingulate (sgACC), and between the sgACC and other
limbic regions. In this study, high frequency rTMS will be used to stimulate the left DLPFC
(recapitulating the therapeutic methodology), specifically, regions of the DLPFC that are
functionally correlated and anti-correlated with the sgACC. This will be accomplished in a
group of patients with MDD, and in a group of carefully matched controls. These subjects
will be scanned before and after rTMS is delivered, as a way of gauging its effects. The
feasibility of this design was recently demonstrated by our group (Eldaief et al. PNAS
2011). Changes induced by the stimulation will be charted with a novel combined MRI-PET
(Positron Emission Tomography) scanner at the MGH Martinos Center, which is capable of
simultaneously recording fcMRI BOLD (Blood oxygenation level-dependent) and
18Flurodeoxyglucose (FDG) PET data. This will permit cortico-limbic networks to be
characterized dynamically through (1) examination of the differential effects of stimulating
two networks in the DLPFC, and (2) by tracking the dynamic interplay between rTMS induced
changes in local glucose metabolism at DLPFC and sgACC on the one hand, and changes in
distributed connectivity between these regions on the other. In an exploratory aim, MDD
patients will return three months later (after they have undergone a non-specific treatment
intervention with their psychiatric provider) for the identical rTMS/fcMRI/FDG-PET
procedures. This aim will establish, as proof of principle, that treatment of MDD is
associated with changes in cortico-limbic functional network architecture, and in
cortico-limbic dynamics. Eventually, it is hoped that this work will lead to the emergence
of aberrant cortical dynamics as a biomarker for MDD. In addition, this work might pollinate
future studies which use aberrant cortical dynamics as a novel therapeutic target upon which
neuromodulatory interventions might intervene.
Inclusion Criteria:
- Ages 18-50
- Patients with Major Depressive Disorder, as confirmed by a referring provider,
DSM-IVR criteria, and/or a Structured Clinical Interview (SCID)
- Score of ≥18 on the 24 item version of the Hamilton Depression Rating Scale (HDRS)
- Meeting criteria to safely receive fMRI scanning, PET scanning and rTMS.
Exclusion Criteria:
- Any subject who is pregnant or lactating
- Patients with bipolar disorder, schizoaffective disorder, suicidal ideation, or any
history of psychosis. Concurrent anxiety disorders will be allowed.
- Any serious concurrent medical or neurological illness
- Any contraindication to receiving TMS, fMRI or PET scans including, but not limited
to having: a pacemaker, metallic implants, implanted pumps, surgical aneurysm clips,
history of severe head trauma, history of seizures or a first degree relative with
epilepsy, been involved in a nuclear medicine study in the past 12 months, diabetes
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Charlestown, Massachusetts 02129
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